The loss of one sensory modality often results in functional enhancement of the remaining senses; this phenomenon is called cross-modal plasticity. The loss of vision specifically can result in better tactile acuity, pitch discriminatin and sound localization in blind individuals. This enhancement can also happen quite quickly, only a few days of blindfold experience can lead to improved Braille reading in normally sighted individuals. These cross-modal changes are correlated with functional recruitment of the visual cortex for processing the remaining senses. While this is beneficial to those affected, it may hinder therapeutic interventions to recover the lost sense. For example, the success of cochlear implants for early deaf people is quite low because extensive cortical reorganization no longer can effectively process auditory stimuli. Our lab reported that depriving rodents of vision alters excitatory synaptic transmission in barrel and auditory cortices. However, regulation of excitatory synaptic transmission represents only half the story of how plasticity mechanisms enhance the remaining senses following visual deprivation. The balance of excitation and inhibition are crucial for normal function in any neuronal circuit. For this reason we hypothesize that changes in excitatory synaptic transmission should also be complemented by inhibitory changes. In addition, this study aims to delineate the molecular mechanisms behind excitatory and inhibitory cross-modal plasticity. By using transgenic mouse models targeting specific activity-regulated gene products (i.e. Arc/Arg3.1 KO and BDNF-KIV KI), which show altered plasticity mechanisms and specifically target excitatory and inhibitory synapses, we can identify if these molecules are important for cross-modal reorganization of neural circuits. Finally, using channel rhodopsin activated parvalbumin neurons, we will investigate the role of this set of inhibitory neurons in cross-modal plasticity. Results from this work will directly impact our understanding of how spared sensory modalities become enhanced following the loss of one sense.